Search

Simple Summary: This research considers means of improving the early detection and treatment of colorectal cancer (CRC), a common and deadly form of cancer often identified too late for effective treatment. In our study, we examined AIFM3, VGLL4, and WNT4 in cancerous and healthy tissues at various stages of CRC. We found that these markers behave differently as the cancer advances. AIFM3 appears in healthy tissue and early cancer stages but disappears as the cancer worsens. VGLL4 increases in the affected tissues as the cancer progresses, particularly noticeable from early to more advanced stages. WNT4 is higher in cancerous tissues, but decreases in the supportive tissue surrounding cancer cells as the disease advances. Low VGLL4 levels are linked to better patient survival, unlike the other two markers. This finding suggests that VGLL4 could be useful as an indicator of CRC prognosis, potentially guiding treatment approaches. Background/Objectives: Colorectal cancer (CRC) remains a significant health burden, and its delayed diagnosis at advanced stages leads to poor survival outcome. Detection of known and novel prognostic markers is essential. In this study, the status of likely prognostic markers—the apoptotic inducing factor (AIFM3), vestigial-like family member 4 (VGLL4), and WNT4—was evaluated. Methods: AIFM3, VGLL4, and WNT4 expression in CRC tissues across different stages (Dukes A–D) were analyzed using histological immunofluorescence staining and RNA sequencing analyses. Results: In advanced CRC stages, progressive loss of normal crypt architecture, reduction of goblet cells, and necrotic debris were detected along with differential expression patterns of AIFM3, VGLL4, and WNT4. AIFM3 exhibited high reactivity in the lamina propria of healthy tissue and Dukes A, but this was diminished in advanced CRC stages. VGLL4 expression, initially confined to the lamina propria, increased significantly in the epithelium of Dukes B and C, with a cytoplasmic localization pattern. WNT4 expression was elevated in the CRC epithelium across all stages, contrasting with a significant reduction in lamina propria reactivity. RNA sequencing corroborated these findings, showing significant downregulation of AIFM3 and WNT4 and upregulation of VGLL4 in CRC tissues compared to controls. Expression of AIFM3 and WNT4 showed no correlation with survival outcome, while low VGLL4 expression was correlated with better survival outcome. Conclusions: The results suggest distinct roles for AIFM3, VGLL4, and WNT4 in CRC progression, highlighting only VGLL4 as a potential prognostic marker. Further evaluation of VGLL4 and its specific role in CRC progression remains to be elucidated. [ABSTRACT FROM AUTHOR]